Department of Radiation Oncology University, Hospital Erlangen, Friedrich-Alexander Universität Erlangen-Nürnberg, Germany.
Autoimmunity. 2013 Aug;46(5):323-8. doi: 10.3109/08916934.2012.747522. Epub 2013 Feb 12.
Since the beginning of the 20th century, low dose radiotherapy (LD-RT) has been practiced and established as therapy of inflammatory diseases. Several clinical studies already have proven the anti-inflammatory effect of low doses of ionizing irradiation (LDR). However, further research is inevitable to reveal the underlying immune-biological mechanisms. Focus has been set on the modulation of activated macrophages by LDR, since they participate in both, initiation and resolution of inflammation. Here we examined with an ex vivo peritoneal mouse macrophage model how LDR modulates the secretion of the inflammatory cytokines IL-1β and TNF-α by activated macrophages and whether the basal radiosensitivity of the immune cells has influence on it. Peritoneal macrophages of Balb/c mice responded to exposure of 0.5 or 0.7 Gy of ionizing irradiation (X-ray) with significant decreased release of IL-1β and slightly, but not significantly, reduced release of TNF-α. Macrophages of the less radiosensitive C57BL/6 mice did not show this anti-inflammatory reaction. This was observed in both wild type and human TNF-α transgenic animals with C57BL/6 background. We conclude that only the inflammatory phenotype of more radiosensitive macrophages is reduced by LDR and that ex vivo and in vivo models with primary cells should be applied to examine how the immune system is modulated by LDR.
自 20 世纪初以来,低剂量放射疗法(LD-RT)已被实践并确立为治疗炎症性疾病的方法。多项临床研究已经证明了低剂量电离辐射(LDR)的抗炎作用。然而,为了揭示潜在的免疫生物学机制,进一步的研究是不可避免的。研究重点集中在低剂量辐射对活化巨噬细胞的调节作用上,因为它们参与了炎症的启动和消退。在这里,我们使用体外腹膜小鼠巨噬细胞模型研究了低剂量辐射如何调节活化巨噬细胞分泌炎症细胞因子 IL-1β 和 TNF-α,以及免疫细胞的基础放射敏感性是否对此有影响。Balb/c 小鼠的腹膜巨噬细胞对 0.5 或 0.7 Gy 电离辐射(X 射线)的暴露反应明显降低了 IL-1β 的释放,并且 TNF-α 的释放略有但无统计学意义的降低。来自放射敏感性较低的 C57BL/6 小鼠的巨噬细胞没有表现出这种抗炎反应。这在具有 C57BL/6 背景的野生型和人 TNF-α 转基因动物中均观察到。我们得出结论,只有更具放射敏感性的巨噬细胞的炎症表型被 LDR 降低,并且应该应用体外和体内原代细胞模型来研究 LDR 如何调节免疫系统。